Nu-(2-tetrahydropyranyl) amides as fungicides



United States Patent 3,293,123 N-(Z-TETRAHYDROPYRANYL) AMIDES ASFUNGICIDES Angelo John Speziale, Creve Coeur, and Gino J. Marco,

Webster Groves, Mo., assignors to Monsanto Company, St. Louis, Mo., acorporation of Delaware No Drawing. Original application Oct. 11, 1961,Ser. No. 144,293. Divided and this application Nov. 10, 1964, Ser. No.410,277

6 Claims. (Cl. 167-33) This application is a division of copendingapplication Serial No. 144,293, filed October 11, 1961.

This invention relates to new and useful N-(Z-tetrahydropyranyl) amidesand to methods of making same.

In accordance with this invention there is provided a new and usefulclass of compounds, namely N-(2-tetrahydropyranyl) amides of the formulawherein R and R are like or unlike hydrocarbyl radicals or saidhydrocarbyl radicals further substituted with substituents such aschloro, ibrorno, nitro, cyano, lower alkoxy, lower alkylthio, di(loweralkyl)amino, and lower alkylcarbonyl. R can also be, and is preferably,hydrogen.

These amides can be prepared in a facile manner by reacting2,3-dihydropyran with an amide of the formula wherein R and R have theabove described significance in the presence of an acid catalyst. Whilea wide range of reaction temperatures can be used provided the system isfluid (i.e. temperatures above the freezing point of the system up toand including the boiling point of the system) it is preferred to employa reaction temperature in the range of from about 30 C. to about 125 C.Where and when desired an inert organic solvent can be used, as forexample benzene, toluene, xylene, acetone, butanone, dioxane,dimethylformamide, dimethylsulfoxide, and the like. In those instanceswherein it is desirable to employ an inert organic solvent it ispreferred to employ a mixture of dirnethylformamide and a liquidaromatic hydrocarbon (e.g. benzene, toluene, xylene, etc.) in the rangein parts by weight of 25 to 75 of the former to 75 to 25 of the latter.

By hydrocarbyl radical as employed herein and in the appended claims ismeant any hydrocarbon radical containing 1 to 12 carbon atoms andincludes the various alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl,aralkyl, aryl and alkaryl radicals the hydrogen substituents of which inthe case of substituted hydrocarbyl radicals being replaced with one ormore substituents such as chloro, bromo, nitro, cyano, lower alkoxy,lower alkylthio, di(lower alkyl)amino, and lower alkylcarbonyl. Asillustrative of such are methyl, ethyl, propyl, butyl, amyl, hexyl,octyl, decyl, dodecyl, allyl, butenyl, pente-nyl, dodecenyl, propargyl,butynyl, cyclopentyl, cyclohexyl, cycloheptyl, methylcyclohexyl,bicyclohexyl, cyclohexylrnethyl, cyclopentenyl, cyclohexenyl, benzyl,phenethyl, phenpropyl, cinnamyl, phenyl, biphenylyl, naphthyl, indanyl,indenyl, tolyl, xylyl, ethylphenyl, butylphenyl, hexylphenyl, and

- the various isomeric forms thereof, and also the substituted formsthereof as for example, chloromethyl, chloroethyl, chloropropyl,chlor-obutyl, chloroallyl, chlorophenyl, ar-chlorobenzyl, bromoethyl,bromophenyl, nitroethyl, nitrobutyl, nitrophenyl, cyanoethyl,cyanobutyl, cyanophen- 3,293,123 Patented Dec. 20, 1966 yl,methoxyethyl, ethoxyethyl, isomyloxyethyl, methoxyphenyl, ethoxyphenyl,isoamyloxyphenyl, methylthioethyl, ethylthioethyl, methylthiophenyl,ethylthiophenyl, isoamylthiophenyl, dimethylamino, diethylamino,diisoamylamino, acetyl, acetonyl, propionyl, butyryl, and the like.

The amide reactants of the process of this invention as aforementionedare of the structure wherein R and R have the aforedescribedsignificance. Of this class of amide reactants several groups fallingtherein provide highly useful N-(Z-tetrahydropyranyl) amides and theyare (A) Those wherein R and R are hydrocarbyl radicals free ofnon-benzenoid unsaturation (i.e. free of olefinic and acetylenicunsaturation) such as the various alkyl, cycloalkyl, and aryl radicalsas exemplified by methyl, ethyl, propyl, butyl, amyl, hexyl, phenyl,cyclopentyl, cyclohexyl, and the various isomeric forms thereofcontaining 1 to 6 carbon atoms,

(B) Those wherein R is hydrogen and wherein R has the significance as in(A) immediately above, and

(C) Those wherein R is hydrogen and wherein R is a primary l-chloroalkylradical containing from 1 to 4 carbon atoms as for examplel-chloromethyl, l-chloroethyl, l-chloro-n-propyl, l-chloro-n-butyl,l-chloro-isobutyl, and the various isomeric forms thereof.

As specifically illustrative of the amide reactants of the process ofthis invention but not limitative thereof are acetamide propionamide,n-butyramide, isobutyrarnide, nvaleramide, n-caproarnide,n-heptanoamide, lauramide, acrylamide, benzamide, p-toluic acid amide,l-naphthoic acid amide, a-phenylacetamide, cyclohexanoamide,benzanalide, acetanilide, N-methylacetamide, N-phenyl-nvaleramide, Ncyclohexyl n-butyramide, a-chloroaceta- Inide, a-chloropropionamide,a-chloroisovaleramide, achloroacetanilide, 4-chlorobenzamide,4-bromobenzarnide, 4 nitrobenzamide, 4 cyanobenzamide, 4methoxybenzamide, b (2 ethoxy(propionamide, 4-(dimethylamino)-benzamide, 4-(acetyl)benzamide, etc.

As illustrative of the process of this invention but not limitativethereof is the following:

Example I To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 11.8 parts by weight(substantially 0.2 mol) of acetamide, 16.8 parts by weight(substantially 0.2 mol) of 2,3-dihydropyran, and approximately 45 partsby weight of benzene, While agitating and at room temperature there isadded approxirnately 0.16 part by weight of hydrogen chloride inapproximately 0.71 part by weight of diethyl ether. The mixture is thenrefluxed for about two hours. Thereafter the reaction mass is cooled toroom temperature and neutralized with solid sodium carbonate. Theneutralized mass is filtered and the filtrate subjected to vacuumdistillation at 60 C. to remove the volatiles. The residue, a solid, isN-(2-tetrahydr0pyranyl) aceta-rnide. Upon recrystallizing this solidfrom a mixture of benzene and diethyl ether the melting point is foundto be 119.5-121" C.

Example II Employing the procedure of Example I but replacing acetamidewith a substantially equi-molecular amount of propionamide there isobtained N-(Z-tetrahydropyranyl) propionamide.

3 Example III Employing the procedure of Example I but replacing:etalmide with a substantially equimolecular amount of'brotmopropionamide there is obtained N(2-tetrahydroydropyranyl)lb-(ethoxymropionarnide.

Example IV Employing the procedure of Example I but replacing :etamidewith a substantially equimolecular amount of -phenylacetamide there isobtained N-(Z-tetrahydroyranyl) a-phenylacetamide.

Example V Employing the procedure of Example I but replacing :etamidewith a substantially equimolecular amount of -(ethoxy)propinamide thereis obtained N-(Z-tetraydropyranyl) b-(ethoxy)propionamide.

Example VI Employing the procedure of Example I but replacing :etamidewith a substantially equimolecular amount of -(ethylthio)propionamidethere is obtained N-(Z-tetravdropyranyl) b-(ethylthio)propionamide.

Example VII To a suitable reaction vessel equipped with a thermomer,agitator and reflux condenser is charged 8.7 parts ,1 weight(substantially 0.1 mol) of isobutyramide, 8.4 arts by weight(substantially 0.1 mol) of 2,3-dihydro- Iran, and approximately 50 partsby weight of benzene. hile agitating and at room temperature there isadded aproxi'mately 0.08 part by weight of hydrogen chlorideapproximately 0.35 part by weight of diethyl ether. he mixture is thenrefluxed for 2 hours. Thereafter the action mass is cooled to roomtemperature, filtered, and .e filtrate subjected to vacuum distillationat 4050 C. I remove the volatiles. The residue, a solid, is N-(2-trahydropyranyl) isobutyramide. Upon recrystallizin-g is solid from abenzene-ether mixture the melting point found to be 111 C.

Example VIII Employing the procedure of Example VII but replacingobutyramide with a substantially equimolecular amount F acrylamide thereis obtained N-(Z-tetrahydropyranyl) :rylamide.

Example IX Employing the procedure of Example VII but replacgisobutyra-mide with a substantially equimolecular mount of4-cyano-n-valeramide there is obtained N-(2- tra hydropyranyl)4-cyano-n-valera1rnide.

Example X Employing the procedure of Example VII but replacgisobutyramide with a substantially equimolecular nount ofN-phenylisobutyramide there is obtained N- etrahydropyranyl)N-phenylisobutyramide.

Example XI To a suitable reaction vessel equipped with a thermomer,agitator and reflux condenser is charged 17.4 parts I Weight(substantially 0.2 mol) of n-butyramide, 16.8 lrts by Weight(substantially 0.2 mol) of 2,3-dihydro- (ran, and approximately 50 partsby weight of benzene. hile agitating and at room temperature there isadded Jproximately 0.16 part by weight of hydrogen chlorideapproximately 0.71 part by weight of diethyl ether. he mixture is thenrefluxed for 2 hours, Thereafter the action mass is cooled to roomtemperature, filtered, and e filtrate subjected to vacuum distillationat 4050-' C. i remove the volatiles. The residue, a solid, is N-(2-trahydropyranyl) n-butyramide. Upon recrystallizing .is solid from etherthe melting point is found to be [.5-525" C.

4 Example XII Employing the procedure of Example XI but replacingn-butyramide with a substantially equimolecular amount of lauramidethere is obtained N-(Z-tetrahydropyranyl) lauramide.

Example XIII Employing the procedure of Example XI but replacingn-butyramide with a substantially equimolecular amount ofb-(acetonyl)propionamide there is obtained N- Z-tetrahydropyranyl) 'b-(acetonyl) propion amide.

Example XIV To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 12.1 parts by weight(substantially 0.1 mol) of benzamide, 8.4 parts by weight (substantially0.1 mol) of 2,3-dihydropyran, and approximately 50 parts by weight ofbenzene. While agitating and at room temperature there is addedapproximately 0.08 part by weight of hydrogen chloride in approximately0.35 part by weight of diethyl ether. The

mixture is then refluxed for 2 hours. Thereafter the reaction mass iscooled to room temperature, filtered, and the filtrate subjectedtovacuum distillation at 4050 C. to remove the volatiles. The residue, asolid, is N-(2- tetrahydropyranyl) benzamide. Upon recrystallizing thissolid from a benzene-ether mixture the melting point is found to be124125 C.

Example XV Employing the procedure of Example XIV but replacingbenzamide with a substantially equi-molecular amount ofN-methyl-benzamide there is obtained N-(Z-tetrahydropyranyl)N-methyl-benzamide.

Example XVI Employing the procedure of Example XIV but replacingbenzamide with a substantially equimolecular amount of 4-cyanobenzamidethere is obtained N(2-tetrahydropyranyl) 4-cyanobenzamide.

Example XVII Employing the procedure of Example XIV but replacingbenzamide with a substantially equimolecular amount of 4-chlorobenzamidethere is obtained N-(Z-tetrabydropyranyl) 4-chlorobenzamide.

Example XVIII To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 6.8 parts by weight(substantially 0.05 mol) of p-toluamide, 4.2 parts by Weight(substantially 0.05 mol) of 2,3-dihydropyran, and a mixture ofapproximately 25 parts by weight of benzene and 25 parts by weight ofdimethylformamide. While agitating and at room temperature there isadded approximately 0.08 part by Weight of hydrogen chloride inapproximately 0.35 part by weight of diethyl ether. The mixture is thenrefluxed for 2 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 60 C. to remove the volatiles. The residue, a solid, is N-(2-tetrahydropyranyl) p-toluamide. Upon recrystallizing this solid from abenzenehexane mixture the melting point is found to be 127-128" C.

Example XIX Employing the procedure of Example XVIII but replacingp-toluamide with a. substantially equimolecular amount of3,4-dichlorobenzamide there is obtained N-(Z- tetrahydropyrany-l)3,4-dichlorobenzamide.

Example XX Employing the procedure of Example XVIII but replacingp-toluamide with a substantially equimolecular amount of4-cthoxybenzamide there is obtained N-(Z- tetrahydropyranyl)4-ethoxybenzarnide.

5. Example XXI Employing the procedure of Example XVIII but replacingp-toluamide with a substantially equimolecular amount of4-(n-butylthio)benzamide there is obtained N- (Z-tetrahydropyranyl)4-(n-butylthio)benzamide.

Example XXII To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 8.3 parts by weight(substantially 0.05 mol) of 4-nitrobenzarnide, 4.2 parts by weight(substantially 0.05 mol) of 2,3-dihydropyran, and a mixture ofapproximately 25 parts by Weight of benzene and 20 parts by weight ofdimethylformamide. While agitating and at room temperature there isadded approximately 0.08 part by weight of hydrogen chloride inapproximately 0.35 part by weight of diethyl ether. The mixture is thenrefluxed for 2 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 60 C. to remove the volatiles. The residue, a solid, isN-(Z-tetrahydropyranyl) 4-nitrobenzamide. Upon recrystallizing thissolid from a benzene-methanol mixture the melting point is found to be179179.5 C.

Example XXIII Employing the procedure of Example XXII but replacing4-nitrobenzamide with a substantially equimolecular amount ofN-phenyl-4-nitrobenzamide there is obtained N-(Z-tetrahydropyranyl)N-phenyl-4-nitrobenzamide.

Example XXIV Employing the procedure of Example XXII but replacing4-nitrobenzamide with a substantially equimolecu'lar amount of3-chloro-4-nitrobenzamide there is obtained N-(tetrahydropyranyl)3-chloro-4-nitrobenzamide.

Example XXV Employing the procedure of Example XXII but replac ing4-nitrobenzamide with a substantially equimolecular amount of4-isoamyloxybenzamide there is obtained N- (tetrahydropyranyl)4-isoamyloxybenzamide.

Example XXVI To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 47 parts by weight(substantially 0.5 mol) of a-chloroacetamide, 42 parts by weight(substantially 0.5 mol) of 2,3-dihydropyran, and a mixture ofapproximately 150 parts by weight of benzene and 50 parts by weight ofdimethylformamide. While agitating and at room temperature there isadded approximately 0.4 part by Weight of hydrogen chloride inapproximately 1.75 parts by weight of diethyl ether. The mixture is thenrefluxed for 2 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 60 C. to remove the volatiles. The residue, a solid, isN-(Z-tet-rahydropyranyl) a-chloroacetamide. Upon recrystallizing thissolid from benzene the melting point is found to be 94-95 C.

Example XXVII Employing the procedure of Example XXVI but replacinga-chloroacetamide with a substantially equimolecular amount ofa-chloro-n-valeramide there is obtained N-(Z-tetrahydropyranyl)a-chloro-n-valeramide.

Example XX VIII Employing the procedure of Example XXVI but replacinga-chloroacetamide with an equimolecular amount of4-(diethylamino)-n-butyramide there is obtained N-(2- tetrahydropyranyl)4-(diethylan1in0)-n-butyrarnide.

Example XXIX Employing the procedure of Example XXVI but replacinga-chloroacetamide with an equimolecular amount 6. of4-nitro-n-butyramide there is obtained N-(Z-tetrahydropyranyl)4-nitro-n-buty-ramide.

Example XXX To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 14.6 parts by weight(substantially 0.1 mol) of N-methyl-acetamide, 17 parts by weight(substantially 0.2 mol) of 2,3-dihydropyran, and approximately 50 partsby weight of benzene. While agitating and at room temperature there isadded approximately 0.08 part by weight of hydrogen chloride inapproximately 0.35 part by weight of diethyl ether. The mixture is thenrefluxed for 17 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 40-50" C. to remove the volatiles. The residue, an oil, is identifiedas N-(Z-tetrahydropyranyl) N-methyl acetarnide by infrared analysis.

Example XXXI Employing the procedure of Example XXX but replacingN-methyl acetamide with a substantially equimolecular amount ofN-cyclohexylacetarnide there is obtained N- (Z-tetrahydropyranyl)N-cyclohexylacetamide.

Example XXXII To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 28 parts by Weight(substantially 0.32 mol) of N-ethyl acetamide, 29 parts by weight(substantially 0.35 mol) of 2,3-dihydropyran, and approximately 75 partsby weight of benzene. While agitating and at room temperature there isadded approximately 0.08 part by Weight of hydrogen chloride inapproximately 0.35 part by Weight of diethyl ether. The mixture is thenrefluxed for 17 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 4050 C. to remove the volatiles. The residue, an oil, which accordingto infrared analysis contains about 45% by weightN-(Z-tetrahydropyranyl) N-ethylacetamide.

Example XXXIII Employing the procedure of Example XXXII but replacingN-ethy-l acetamide With a substantially equimolecular amount ofN-(Z-chloroethyl) acetamide there is obtained N-(Z-tetrahydropyranyl)N-(2-chloroethyl) acetamide.

Example XXXIV To a suitable reaction vessel equipped with a thermometer,agitator and reflux condenser is charged 13.5 parts by weight(substantially 0.1 mol) of N-phenyl acetamide, 10 parts by weight(substantially 0.12, mol) of 2,3-dihydropyran, and approximately 50parts by weight of benzene. While agitating and at room temperaturethere is added approximately 0.08 part by weight of hydrogen chloride inapproximately 0.35 part by weight of diethyl ether. The mixture is thenrefluxed for 16 hours. Thereafter the reaction mass is cooled to roomtemperature, filtered, and the filtrate subjected to vacuum distillationat 4050 C. to remove the volatiles. The residue, and oil, whichaccording to infrared analysis contains about 35% by weightN-(Z-tetrahydropyranyl) N-phenylaoetamide.

Example XXX V Employing the procedure of Example XXXIV but replacingN-phenyl acetamide with a substantially equirnolar amount of benzanilidethere is obtained N-(Z-tetrahydropyranyl) benzanilide.

Other acid catalysts than hydrogen chloride which are operable includethe strong mineral acids such as hydrogen bromide, sulfuric acid, andthe like, and the aromatic sulfonic acids such as benzene sulfonic acid,p-toluene sulfonic acid, and the like. Any catalytic amount of 1e acidcatalyst can be used but in general from 0.01 to percent by weight basedon the 2,3-dihydropyran charged ill be employed in preparing theN-(Z-tetrahydropyranyl) rnides of this invention.

The N-(Z-tetrahydropyranyl) amides of this invention re useful as soiland/or foliage fungicides. To illusate their activity is the following:

Quadruplet cucumber plants (14 to 21 days old) having 1e first leaf thesize of a half-dollar are sprayed to run-off with an aqueous emulsioncontaining 1250 p.p.m. f N-(Z-tetrahy-dropyranyl) N-methylacetamide at arate f 10 ml. per 45 seconds using 10 pounds air pressure 'hile rotatingthe plants on a turntable in a spray chamer. For control purposes oneleaf of each plant is avered with a plastic shield prior to spraying.After Jraying to run-off the spray deposit i permitted to ry and thetreated and untreated leaves of each plant re sprayed with a sporesuspension containing 30,000 40,000 conidal spores of Colletotrichumlangenarium er ml. The so-inoculated plants are placed immediately 1 a100% humid atmosphere at 70 C. After 36 hours 1e plants are removed tothe greenhouse. After 3 to days lesion counts are made on the first leafof each lant. There were no :lesions on the first leaf of each lanttreated with N-(Z-tetrahydropyranyl) N-methylcetamide however therespective control or untreated :aves displayed more than 50 lesions perleaf.

The new compounds are also valuable fungicides gainst soil-bornepathogens. Activity was demonstrated y pipetting a 5 ml. aliquot of a 1%solution of the :st material into a Mason jar containing one pound ofrfected soil. This amounts to 100 p.p.m. of the test taterial. The jarwas sealed and the contents thoroughly nixed by vigorous shaking. Thetreated soil was in- Jbated at room temperature and 24 hours latertrans- :rred to 4 inch clay pots. Five seeds of each of four ropplants,beans, cotton, cucumber and peas, were )wn in each pot. The seeded potswere then incubated t 70 F. and at high humidity (98% RH.) to insurectivity of the damping-off organisms in the soil. 'wenty-four hourslater, the pots were removed to a reenhouse where disease assessmentswere made -14 ays later. The percent emergence and disease incidence 'asrecorded. The measure of effectiveness was the umber of healthy plantsemerging out of 20. Ten or :ss healthy plants are observed with anuntreated conotl and therefore a test material giving a sum of 11 or :ssis regarded as inactive whereas more than 17 is ited excellent, 15-17promising and 12-14 fair. The gures in the table below are averages oftwo replications.

Healthy plants est material: out of N-(2-tetrahydropyranyl)a-chloroacetamide 16 N (2-tetrahydropyranyl) N-phenylacetamide 16Untreated control 2 The compounds of this invention were also observedbe wheat rust eradicants, particularly N-(Z-tetrahydroyranyl) benzamide.

Although the novel fungicidal agents of this invention re useful per sein controlling a wide variety of fungal rganisms, it is preferable thatthey be supplied to the rganisms or to the environment of the organismsin a ispersed form in a suitable extending agent.

In the instant specification and appended claims it is be understoodthat the term dispersed is used in its 'idest possible sense. When it issaid that the fungicidal gents of this invention are dispersed, it meansthat the articles of the fungicidal agents of this invention may beiolecular in size and held in true solution in a suitable rganicsolvent. It means further, that the particles my e colloidal in size anddistributed throughout a liquid hase in the form of suspensions oremulsions or in the arm of particles held in suspension by wettingagents. t also includes particles which are distributed in a semisolidviscous carrier such as petrolatum or soap or other ointment base inwhich they may be actually dissolved in the semi-solid or held insuspension in the semi-solid with the aid of suitable wetting oremulsifying agents. The term dispersed also means that the particles maybe mixed with and distributed throughout a solid carrier providing amixture in particulate form, e.g. pellets, granules, powders, or dusts.The term dispersed also includes mixtures which are suitable for use asaerosols including solutions, suspensions, or emulsions of thefungicidal agents of this invention in a carrier such asdichloro-difiuoromethane and like fluorochloroalkanes which boil belowroom temperature at atmospheric pressure.

In the instant specification and appended claims it is to be understoodthat the expression extending agent includes any and all of thosesubstances in which the fungicidal agents of this invention aredispersed. It includes, therefore, the solvents of a true solution, theliquid phase of suspensions, emulsions or aerosols, the semi-solidcarrier of ointments and the solid phase of particulate solids, e.g.pellets, granules, dusts and pow ders.

The exact concentration of the fungicidal agents of this inventionemployed in combatting or controlling fungal organisms can varyconsiderably provided the required dosage (i.e., toxic or lethal amount)thereof is supplied to the organisms or to the environment of theorganisms. When the extending agent is a liquid or mixture of liquids(e.g. as in solutions, suspensions, emulsions, or aerosols) theconcentration of the fungicidal agent employed to supply the desireddosage generally will be in the range of 0.001 to 50 percent by weight.When the extending agent is a semi-solid or solid, the concentration ofthe fungicidal agent employed to supply the desired dosage generallywill be in the range of 0.1 to 25 percent by weight. From a practicalpoint of view, the manufacturer must supply the agriculturist with alowcost concentrate or spray base or particulate solid base in such formthat, by merelymixing with water or solid extender (e.g., powdered clayor talc) or other low-cost material avail-able to the agriculturist atthe point of use, he will have an easily prepared fungicidal spray orparticulate solid. In such a concentrate composition, the fungicidalagent generally will be present in a concentration of 5 to 95 percent byweight, the residue being any one or more of the well-known fungicidaladjuvants, such as the various surface active agents (e.g. detergents, asoap or other emulsifying or wetting agent, surface-active clays),solvents, diluents, carrier media, adhesives, spreading agents,hu'mectants, and the like.

There are a large number of organic liquids which can be used for thepreparation of solutions, suspensions, or emulsions of the fungicidalagents of this invention. For example, isopropyl ether, acetone, methylethyl ketone, dioxane, cyclohexanone, carbon tetrachloride, ethylenedichloride, tetrachloroethane, hexane, heptane and like higher liquidalkanes, hydrogenated naphthalenes, solvent naphtha, benzene, toluene,xylene, petroleum fractions (e.g. those boiling almost entirely under400 F., at atmospheric pressure and having a flash point above about F.,particularly kerosene), mineral oils having an unsulfontable residueabove about 80 percent and preferably above about percent. In thoseinstances wherein there may be concern about the phytoxicity of theorganic liquid extending agent a portion of same can be replaced by suchlow molecular Weight aliphatic hydrocarbons as dipentene, diisobutylene,propylene trimer, and the like or suitable polar organic liquids such asthe aliphatic ethers and the aliphatic ketones containing not more thanabout 10 carbon atoms as exemplified by acetone, methyl ethyl ketone,diisobutyl ketone, dioxane, isopropyl ether, and the like. In certaininstances, it is advantageous to employ a mixture of organic liquids asthe extending agent.

Whenthe fungicidal agents of this invention are to be supplied to thefungal organisms or to the environrnent of the organisms as aerosols, itis convenient to dissolve them in a suitable solvent and disperse theresulting solution in dichlorodifluoromethane or like chlorofluoroalkanewhich boils below room temperature at atmospheric pressure.

The fungicidal agents of this invention are preferably supplied to thefungal organisms or to the environment of the organisms in the form ofemulsions or suspensions. Emulsions or suspensions are prepared bydispersing one or more fungicidal agents of this invention either per seor in the form of an organic solution thereof in Water with the aid of awater-soluble surfactant. The term surfactant as employed here and inthe appended claims is used as in volume II of Schwartz, Perry andBerchs Surface Active Agents and Detergents (1958, IntersciencePublishers, Inc., New York) in place of the expression emulsifying agentto connote generically the various emulsifying agents, dispersingagents, wetting agents and spreading agents that are adapted to beadmixed with the fungicidal agents of this invention in order to securebetter wetting and spreading of the active ingredients in the watervehicle or carrier in which they are insoluble through lowering thesurface tension of the Water (see also Frear Chemistry of Insecticides,Fungicides and Herbicides, second edition, page 280). These surfactantsinclude the Well-known capillary-active substances which may beanion-active (or anionic), cation active (or cationic), or non-ionizing(or non-ionic) which are described in detail in volumes I and II ofSchwartz, Perry and Berchs Surface Active Agents and Detergents (1958Interscience Publishers, Inc., New York) and also in the November 1947issue of Chemical Industries (pages 811-824) in an article entitledSynthetic Detergents, by John W. McCutcheon, and also in the July,August, September and October 1952 issues of Soap and Sanitary Chemicalsunder the title Synthetic Detergents. The disclosures of these articleswith respect to surfactants, i.e. the anion active, cation-active andnon-ionizing capillary-active substances, are incorporated in thisspecification by reference in order to avoid unnecessary enlargement ofthis specification. The preferred surfactants are the Water-solubleanionic surface-active agents and the water soluble non-ionicsurface-active agents set forth in U.S. 2,846,398 (issued August 5,1958). In general it is preferred that a mixture of water-solubleanionic and water-soluble non-ionic surfactants be employed.

The fungicidal agents of this invention can be dispersed :by suitablemethods (e.g., tumbling or grinding) in solid extending agents either oforganic or inorganic nature and supplied to the fungal organismsenvironment in particulate form. Such solid materials include forexample, tricalcium phosphate, calcium carbonate, kaolin, bole,kieselguhr, talc, bentonite, fullers earth, pyrophillite diatomaceousearth, calcined magnesia, volcanic ash, sulfur and the like inorganicsolid materials, and include, for example, such materials of organicnature as powdered cork, powdered Wood, and powdered Walnut shells. Thepreferred solid carriers are the adsorbent clays, e.g. bentonite. Thesemixtures can be used for fungicidal purposes in the dry form, or, byaddition of water-soluble surfactants or wetting agents the dryparticulate solids can be rendered wettable by water so as to obtainstable aqueous dispersions or suspensions suitable for use as sprays.

For special purposes the fungicidal agents of this invention can bedispersed in a semi-solid extending agent such as petrolatum or soap(e.g., sodium stearate or oleate or palrnitate or mixtures thereof) withor without the aid of solubility promoters and/or surfactants ordispersing agents.

In all of the forms described above the dispersions can be providedready for use in combating fungal organisms or they can be provided in aconcentrated form suitable for mixing with or dispersing in otherextending agents. As illustrative of a particularly useful concentrateis an intimate mixture of one or more fungicidal agents of thisinvention with a water-coluble surfactant which lowers the surfacetension of water in the weight proportions of 0.1 to 15 parts ofsurfactant with suflicient of the fungicidal agent of this invention tomake 100 parts by weight. Such a concentrate is particularly adapted tobe made into a spray for combatting various forms of fungal organisms bythe addition of water thereto. As illustrative of such a concentrate isan intimate mixture of parts by weight of N-(Z-tetrahydropyranyl)N-methylacetamide and 5 parts by Weight of a water-soluble non-ionicsurfactant such as the polyoxyethylene derivative of sorbitanmonolaurate.

Another useful concentrate adapted to be made into a spray forcombatting fungal organisms is a solution (preferably as concentrated aspossible) of one or more fungicidal agents of this invention in anorganic solvent therefor. The said liquid concentrate preferablycontains dissolved therein a minor amount (e.g., 0.5 to 10 percent byweight of the weight of the new fungicidal agent) of a surfactant (oremulsifying agent), which surfactant is also water-soluble. Asillustrative of such a concentrate is a solution ofN-(Z-tetrahydropyranyl) N- methylacetamide in acetone which solutioncontains dissolved therein a water-soluble polyoxyethylene glycolnon-ionic sufactant and a Water-soluble alkylaryl sulfonate anionicsurfactant.

Of the surfactants aforementioned in preparing the I variousemulsifiable, wettable or dispersible compositions or concentrates ofthis invention, the amionic and nonionic surfactants are preferred. Ofthe anionic surfactants, the particularly preferred are well-knownwater-soluble alkali metal alkylaryl sulfonates as exemplified bysodiurn decylbenztene sulfonate and sodium dodecylbenzene sulfonate. Ofthe non-ionic surfactants, the particularly preferred are thewater-soluble polyoxyethylene derivatives of alkylphenols (particularlyisooctylphenol) and the water-soluble polyoxyethylene; derivatives ofthe mono-higher fatty acid esters of hexital anhydrides such as mannitanor sorbitan.

In all of the various dispersions described hereinbefore for fungicidalpurposes, the active ingredients can be one or more of the compounds ofthis invention. The compounds of this invention can also beadvantageously employed in combination with other pesticides, including,for example, insecticides, nematocides, ba'cterocides, and herbicides.In this manner it is possible to obtain mixtures which are effectiveagainst a wide variety of pests and other forms of noxious life.

In controlling or combatting fungal organisms the fungicidal agents ofthis invention either per se or compositions comprising same aresupplied to the fungal organisms or to their environment in a lethal ortoxic amount. This can be done by dispersing the new fungicidal agent orfungicidal composition comprising same in, on or over an infestedenvironment or in, on or over an environment the fungal organismsfrequent, e.g. agricultural soil or other growth media or other mediainfested with the fungal organisms or attractable to the organisms forhabitational or sustenance or propagational purposes, in anyconventional fashion which permits contact between the organisms and thefungicidal agents of this invention. Such dispersing can be broughtabout by applying the fungicidal agent per se or sprays or particulatesolid compositions containing same to a surface infested with the fungalorganisms or attractable to the organisms as for example, the surface ofagricultural soil or other media such as the above ground surface ofplants by any of the conventional methods, e.g. power dusters, boom andhand sprayers, and spray dusters. Also for sub-surface application suchdispersing :an be carried out :by simply mixing the new fungicidal agentper se or fungicidal spray or particulate solid :ompositions comprisingsame with the infested environnent or with the environment the fungalorganisms frequent, or by employing a liquid carrier for the newFungicidal agent to accomplish sub-surface penetration 1nd impregnationtherein.

What is claimed is: I

1. The method of controlling fungal growth which omprises contacting thesaid fungus with a fungicidal amount of an N-(Z-tetrahydropyranyl) amideof the ormula Ihezrein R is selected from the group consisting of (l).ydrocarbyl containing from 1 to 6 carbon atoms and is ree ofnonbenzenoid unsaturation and (2) primary -chloroalkyl containing from 1to 4 carbon atoms, and heroin R is selected from the :group consistingof hyrogen and hydrocarbyl containing from 1 to 6 carbon toms and isfree of non-benzenoid unsaturation, but ihen R is primary l-chloroalkylthen R is hydrogen.

2. The method of controlling fungal growth which omprises contacting thesaid fungus with a fungicidal mount of an N-(Z-tetrahydropyranyl) amideof the ornmla wherein R is hydrocarbyl containing from 1 to 6 carbonatoms and is free of non-benzen-oid unsaturation.

3. The method of controlling fungal growth which comprises contactingthe said fungus with a fungicidal amount of an N-(Z-tetrahydropyranyl)amide of the No references cited.

JULIAN S. LEVITT, Primary Examiner.

VERA C. CLARKE, Assistant Examiner.

1. THE METHOD OF CONTROLLING FUNGAL GROWTH WHICH COMPRISES CONTACTINGTHE SAID FUNGUS WITH A FUNGICIDAL AMOUNT OF AN N-(2-TETRAHYDROPYRANYL)AMIDE OF THE FORMULA